This application is in the general field of therapeutic electrical energy delivery, and it pertains more specifically to electrical energy delivery in the context of ablation of nerves in the vascular or vessel walls of renal arteries or renal denervation, a therapeutic procedure that can lead to reduced hypertension in patients with high blood pressure. The ablation energy can be in the form of high voltage DC pulses that generate irreversible electroporation of cell membranes and destroy tissue locally for therapeutic purposes, or it can be applied as RF energy that generates thermal energy.
The past two decades have seen advances in the technique of electroporation as it has progressed from the laboratory to clinical applications. Known methods include applying brief, high voltage DC pulses to tissue, thereby generating locally high electric fields, typically in the range of hundreds of Volts/centimeter. The electric fields disrupt cell membranes by generating pores in the cell membrane, which subsequently destroys the cell membrane and the cell. While the precise mechanism of this electrically-driven pore generation (or electroporation) awaits a detailed understanding, it is thought that the application of relatively large electric fields generates instabilities in the phospholipid bilayers in cell membranes, as well as mitochondria, causing the occurrence of a distribution of local gaps or pores in the membrane. If the applied electric field at the membrane exceeds a threshold value, typically dependent on cell size, the electroporation is irreversible and the pores remain open, permitting exchange of material across the membrane and leading to apoptosis or cell death. Subsequently, the surrounding tissue heals in a natural process.
While pulsed DC voltages are known to drive electroporation under the right circumstances, the examples of irreversible electroporation applications in medicine and delivery methods described in the prior art do not provide specific means of limiting possible damage to nearby tissue while it is desired to ablate tissue relatively farther away. There is a need for selective energy delivery methods and devices that generate tissue ablation where it is desired, while leaving tissue elsewhere relatively intact and unchanged. In the specific context of minimally invasive renal denervation for the treatment of hypertension, known ablation devices are generally positioned in the renal arteries for electrical energy delivery to the renal artery walls. The outer layers of the renal arteries, or adventitia, have a distribution of renal nerve endings. When these nerve endings are destroyed by application of a high electric field, the consequent reduction in renal sympathetic activity can result in decreased hypertension. During this process, the vessel wall must be maintained intact; the local electric field in the vessel wall must not be too large, in order to avoid generating locally large current densities in the vessel wall which can lead to local thermal “hot spots” that can unintentionally damage or perforate the renal vessel. Thus it is desired to maintain vessel integrity and reduce and/or avoid local thermal hot spots driven by locally large current densities while still maintaining an electric field magnitude that is still above the threshold of irreversible electroporation.
There is a need for selective energy delivery for electroporation in such a manner as to preserve overall vascular integrity while destroying the nerve endings in the adventitia of the renal artery where ablation is to be performed.